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Ketamine salts solubility

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AlsoTapered said:
BTW Why are you moving the amine away from the aryl moiety? Note dizocilpine, the prototype NMDA antagonist or diphenidine. Their has to be an aryl just 1 methylene from the aryl. Identify the key moieties and consider their spatial relationship (including the N:).

The first effort was so close - just the LogP which, BTW, you could have brought down by adding a ketone. Where? Dunno.
Click to expand...
Pure curiosity, I knew it would get rid of the NMDA activity.

I messed around with diphenidine analogues for awhile after that post. And methylphenidate analogues. Found a few interesting molecules, turns out methylphenidate analogues with a cyclohexyl in place of the acetate can have 5HT-2a activity. Might upload the images later.

Adding a ketone was my first idea, tried a couple positions, didn't work out. Didn't try every position, tho. Can't stick it in the "classic" position without resulting in a Texas carbon or course.
 
If you followed the patents, the MOST potent is 1-[(3S,4S)-3-methyl-4-(thiophen-2-yl)thian-4-yl]piperidine which has sub-nM affinity.

Don't confuse affinity and activity. a drug can be anywhere from a superagonist to an antagonist, That said, Ralf Helm has already explored the phenylpiperidine class and produced some very potent 5HT2a agonists,

A good lesson is to read what has already been done. If you draw something and copy it's SMILES definition into PubChem, if it's known, it spits out the papers and patents.

Almost everything that SEEMS obvious will also seem obvious to a researcher...who has a lab.

Yes in-silico design is possible, but you need ChemOffice and access to Reaxys at least.

The former I was gifted, the latter... I know people at Imperial Collage (who have unlimited Reaxys searches)

TBH read all of the papers and patents you can find. We added a thread that is called 'Useful neuroscience/pharmacology threads'
and it has books, papers and articles. Hundreds of them. And those were chosen carefully. No fat. It's ALL useful.

No point in re-inventing the wheel. LOOK at how researchers work by finding the original patent of a drug:

I use a Japanese language site but their is a cheat: I google 'drugfuture.com chlorodiazepoxie' (if I want the chlorodiazepoxide papers and patents and returns them in English thus:


Then you use Google Patents, it will tell you all later patents that reference the one you are reading so you can quickly see how a class was developed,

PubChem sometimes doesn't have as much but it might be easier for you.

pubchem.ncbi.nlm.nih.gov

PubChem

PubChem is the world's largest collection of freely accessible chemical information. Search chemicals by name, molecular formula, structure, and other identifiers. Find chemical and physical properties, biological activities, safety and toxicity information, patents, literature citations and more.
pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov

But either way - look at each of the classes of commonly abused drugs. You will soon see how it all works.
 
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AlsoTapered said:
If you followed the patents, the MOST potent is 1-[(3S,4S)-3-methyl-4-(thiophen-2-yl)thian-4-yl]piperidine which has sub-nM affinity.

Don't confuse affinity and activity. a drug can be anywhere from a superagonist to an antagonist, That said, Ralf Helm has already explored the phenylpiperidine class and produced some very potent 5HT2a agonists,

A good lesson is to read what has already been done. If you draw something and copy it's SMILES definition into PubChem, if it's known, it spits out the papers and patents.

Almost everything that SEEMS obvious will also seem obvious to a researcher...who has a lab.

Yes in-silico design is possible, but you need ChemOffice and access to Reaxys at least.

The former I was gifted, the latter... I know people at Imperial Collage (who have unlimited Reaxys searches)

TBH read all of the papers and patents you can find. We added a thread that is called 'Useful neuroscience/pharmacology threads'
and it has books, papers and articles. Hundreds of them. And those were chosen carefully. No fat. It's ALL useful.

No point in re-inventing the wheel. LOOK at how researchers work by finding the original patent of a drug:

I use a Japanese language site but their is a cheat: I google 'drugfuture.com chlorodiazepoxie' (if I want the chlorodiazepoxide papers and patents and returns them in English thus:


Then you use Google Patents, it will tell you all later patents that reference the one you are reading so you can quickly see how a class was developed,

PubChem sometimes doesn't have as much but it might be easier for you.

pubchem.ncbi.nlm.nih.gov

PubChem

PubChem is the world's largest collection of freely accessible chemical information. Search chemicals by name, molecular formula, structure, and other identifiers. Find chemical and physical properties, biological activities, safety and toxicity information, patents, literature citations and more.
pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov

But either way - look at each of the classes of commonly abused drugs. You will soon see how it all works.
Click to expand...
I mean delete this thread then, what's it even for in that case? Lol
 
AlsoTapered said:
A good lesson is to read what has already been done. If you draw something and copy it's SMILES definition into PubChem, if it's known, it spits out the papers and patents.
Click to expand...
Btw, I did try that with many of the compounds I drew, and found nothing.

And also, nitpicky note, but the psychedelics I posted were not piperidines.
 
pharmakos said:
Is this a known class of compounds? Did one of my usual amateur ideas I tend to do when I'm playing around with SAR, noticed that moving that nitrogen "over" one gives a phenethylamine skeleton. First attempt showed decent transporter binding. Played around with all the obvious substitutions til I landed on this.



CNC(C)C1(CCCCC1)C1=CC=CC(F)=C1
1-[1-(3-fluorophenyl)cyclohexyl]-N-methylethanamine
LogP 3.8

The 4-trifluoromethyl has slightly better binding predicted, but a less favorable LogP, 4.47.

Lots of the other obvious substitutions one would think of for phenethylamines also work (i.e. alkyl instead of fluoro, longer alkyl groups on the "alpha" carbon or the nitrogen, removing those carbon atoms, etc). These two^ were the ones with the most favorable predictions for transporter binding tho.

4-methyl is the only substitution that adds 5-HT2a activity.



CC1=CC=C(C=C1)C1(CN)CCCCC1
[1-(4-methylphenyl)cyclohexyl]methanamine
LogP 3.81
Click to expand...

I should have systematically saved the SMILES formulas for the rest of that post, rather than needing to rebuild the structure if I want to revisit them. These two, however, go ahead and Google search and you will find next to nothing. A few generic pages with the structure, pages so generic that I'm quite sure they were generated by systematic algorithmic automation, rather than by a human hand directly. No research or anything past that.

Chemistry is a big world, not everything has been tried by any means, not even close. There's a reason that AI is being used to quickly churn through ideas, because the iceberg is that big, and we've only just seen the tip of it. With AI we may someday reach a point where the "throwing shit at the wall and hoping it sticks" method like this is pointless. But we are surely not there yet.
 
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AlsoTapered said:
I clearly wasn't replying to you.
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Huh? Genuinely wasn't clear if so. Your post functioned when considered as a response to my post directly before it... just looked like you quoted the wrong post. The post you quoted originally replying to wasn't even talking about SAR...
 
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Well, I guess you don't want to hear about my craziest idea. Making an amphetamine out of Guaifenesin. All you would have to do is add an amphetamine link to Guaifenesins molecular structure. It could possibly work. Just take a look at the molecule.
 
What's the big difference between 3,4 Ethylene Dioxy Methamphetamine and 3,4 Dioxane Methamphetamine ? Because they almost look the same.
 
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Here's another one I came up with. Its chemical name is -1-(1,3-Benzodioxol-5-yl)-1-phenylpropan-1-amine. Its closely related to MDA.
 
pmzapGuXp
pnvD6N0Ap
Heres a couple pictures of my designs. The first is THC crossed with a tryptamine I call it tetryptamine. The second is a molecule I call MDA1. https://imageshack.com/i/pmzapGuXp https://imageshack.com/i/pnvD6N0Ap
 
If you're associated with an institution, most university libraries have a system where articles that the library doesn't have access to can be requested usually called interlibrary loan and it works with books as well. They've been able to get me papers within a few days 99%+ of the time with a simple request
 
1-(4-carbmethoxyphenyl)-2-aminopropane.png


JUICY_FRUIT
1-(4-carbmethoxyphenyl)-2-aminopropane

1-(5-hydroxyindole-3-yl)-2-aminopropane.png


AMS
Alpha Methyl Serotonin
1-(5-hydroxyindole-3-yl)-2-aminopropane


Then again, maybe not. I did not enjoy AMT, And ring hydroxylated amphetamines are not particularly desirable.
 
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negrogesic said:
On a side note Sekio isn't a she, but do you guys remember the user Nuke from what was once known as Advanced Drug Discussion? I believe @nuke was a she.
Click to expand...

@nuke was indeed a she and smart as hell too. She is in a ton of the early threads in PD talking about all RCs that were first hitting the market in the old days, all of the classic Tryps and Phens that laid the groundwork for what the scene became down the road. Havent seen her on here in many years.
 
1-(3-methoxyphenyl)-N-cyclohexyl-1-aminocyclohexane.png


MEINEKEE
1-(3-methoxyphenyl)-N-cyclohexyl-1-aminocyclohexane

Maybe it's Meinekee!
 
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